PMID- 16645141
OWN - NLM
STAT- MEDLINE
DCOM- 20060628
LR  - 20131121
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 98
IP  - 11
DP  - 2006 Jun 9
TI  - Erythropoietin-mobilized endothelial progenitors enhance reendothelialization via 
      Akt-endothelial nitric oxide synthase activation and prevent neointimal 
      hyperplasia.
PG  - 1405-13
AB  - We investigated whether the mobilization of endothelial progenitor cells (EPCs) 
      by exogenous erythropoietin (Epo) promotes the repair of injured endothelium. 
      Recombinant human Epo was injected (1000 IU/kg for the initial 3 days) after wire 
      injury of the femoral artery of mice. Neointimal formation was inhibited by Epo 
      to 48% of the control (P<0.05) in an NO-dependent manner. Epo induced a 1.4-fold 
      increase in reendothelialized area of day 14 denuded vessels, 55% of which was 
      derived from bone marrow (BM) cells. Epo increased the circulating 
      Sca-1(+)/Flk-1(+) EPCs (2.0-fold, P<0.05) with endothelial properties NO 
      dependently. BM replacement by GFP- or beta-galactosidase-overexpressing cells 
      showed that Epo stimulated both differentiation of BM-derived EPCs and 
      proliferation of resident ECs. BM-derived ECs increased 2.2- to 2.7-fold (P<0.05) 
      in the Epo-induced neoendothelium, where the expression of Epo receptor was 
      upregulated. Epo induced Akt/eNOS phosphorylation and NO synthesis on EPCs and 
      exerted an antiapoptotic action on wire-injured arteries. In conclusion, Epo 
      treatment inhibits the neointimal hyperplasia after arterial injury in an 
      NO-dependent manner by acting on the injured vessels and mobilizing EPCs to the 
      neo-endothelium.
FAU - Urao, Norifumi
AU  - Urao N
AD  - Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, 
      Kyoto 602-8566, Japan.
FAU - Okigaki, Mitsuhiko
AU  - Okigaki M
FAU - Yamada, Hiroyuki
AU  - Yamada H
FAU - Aadachi, Yasushi
AU  - Aadachi Y
FAU - Matsuno, Kuniharu
AU  - Matsuno K
FAU - Matsui, Akihiro
AU  - Matsui A
FAU - Matsunaga, Shinsaku
AU  - Matsunaga S
FAU - Tateishi, Kento
AU  - Tateishi K
FAU - Nomura, Tetsuya
AU  - Nomura T
FAU - Takahashi, Tomosaburo
AU  - Takahashi T
FAU - Tatsumi, Tetsuya
AU  - Tatsumi T
FAU - Matsubara, Hiroaki
AU  - Matsubara H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060427
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Receptors, Erythropoietin)
RN  - 0 (Recombinant Proteins)
RN  - 11096-26-7 (Erythropoietin)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
CIN - Circ Res. 2006 Jun 9;98(11):1341-3. PMID: 16763168
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Bone Marrow Cells/metabolism/pathology
MH  - *Bone Marrow Transplantation
MH  - Cell Movement/drug effects
MH  - Cells, Cultured
MH  - Endothelium, Vascular/pathology/*physiopathology
MH  - Enzyme Activation
MH  - Erythropoietin/*pharmacology
MH  - Femoral Artery/injuries/metabolism
MH  - Humans
MH  - Hyperplasia/prevention & control
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type III/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Receptors, Erythropoietin/metabolism
MH  - Recombinant Proteins
MH  - Tunica Intima/drug effects/*pathology
MH  - Wound Healing/*drug effects
MH  - Wounds and Injuries/metabolism/physiopathology
EDAT- 2006/04/29 09:00
MHDA- 2006/06/29 09:00
CRDT- 2006/04/29 09:00
PHST- 2006/04/29 09:00 [pubmed]
PHST- 2006/06/29 09:00 [medline]
PHST- 2006/04/29 09:00 [entrez]
AID - 01.RES.0000224117.59417.f3 [pii]
AID - 10.1161/01.RES.0000224117.59417.f3 [doi]
PST - ppublish
SO  - Circ Res. 2006 Jun 9;98(11):1405-13. doi: 10.1161/01.RES.0000224117.59417.f3. 
      Epub 2006 Apr 27.